Endotypes of difficult-to-control asthma in inner-city African American children

Abstract

African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6–17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population.

A strategy for high‐dimensional multivariable analysis classifies childhood asthma phenotypes from genetic, immunological, and environmental factors

“…This study contains a novel proposal for prediction analyses of childhood asthma using cytokine, genotype, flow cytometry, diagnostic, questionnaire, RT‐PCR, and microarray data simultaneously. Many studies on childhood asthma currently analyze phenotypes based on assessment of singular measurements only …”

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

“…In addition, filaggrin mutations seem to play a less pathogenic role in patients of African origin than in individuals of European or Asian ancestry (45). In inner-city African American children, CXCL1, IL-5, IL-8, and IL-17A were positively associated with difficult-to-control asthma, while IL-4 and IL-13 were positively associated with easy-to-control asthma (46).…”

Cytokine levels in children and adults with wheezing and asthma show specific patterns of variability over time

“…Recently, Brown and colleagues enrolled 235 asthmatic children and quantified 38 serum cytokine levels using a multiplex assay. They identified chemokine (C‐X‐C motif) ligand (CXCL)‐1, IL‐5, IL‐8 and IL‐17 in inner‐city African American children, which were positively associated with ‘easy‐to‐control’ asthma [7]. In adults with atopic asthma, elevated T2 cytokine responses (IL‐4, IL‐5, IL‐13) to allergenic and antigenic stimuli were observed compared to non‐atopic asthmatics [8].…”